Microglia are a hematopoetic-derived population of cells that make up 20% of the non-neuronal cells in the brain, and function both as neuronal support and as the macrophage-like resident immune cells. During acute brain pathology, substances secreted by damaged or dying cells can cause activation of microglia resulting in microglia-orchestrated neuroinflammation that can exacerbate pathological brain damage. We hypothesize that ion channel function is involved in microglia activation by maintaining membrane potential (Vm) and/or promoting dynamic, oscillatory changes in Vm. This hypothesis is based on our laboratory's finding that blocking specific ion channels inhibits microglia activation, and on my results showing that the same channels promote Vm oscillations. In this proposal, I will use electrophysiological, several types of single-cell flourescence imaging, and cellular functional assays to assess the role of Vm in microglia activation. In particular, I will focus on intracellular calcium regulation and chemotaxis. The ultimate goal of our studies is to gain an understanding of how to regulate microglia activation, possibly leading to novel treatment of brain pathologies.